Cross-comparison of patient-derived xenografts and derivative organoids and cell lines for translational research in hepatocellular carcinoma

患者来源的异种移植物和衍生类器官和细胞系的交叉比较,用于肝细胞癌的转化研究

基本信息

  • 批准号:
    10041707
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide with more than 745,000 fatalities in 2012 alone. The majority of patients with HCC present with unresectable disease at diagnosis and a life expectancy of less than 20 months, with only 15% of these patients surviving more than one year after diagnosis. This dismal prognosis underscores the limited therapeutic options for these patients. HCC is a notoriously chemoresistant malignancy and advances in targeted therapeutics have been unsuccessful in improving survival resulting in what some have called “a losing battle” in the development of therapies. This deficiency issues, in large part, from limitations of current preclinical models in (i) recapitulating the inter- and intra-tumoral heterogeneity that characterizes HCC and (ii) predicting patient response to therapeutics. While patient-derived tumor models have been demonstrated to more faithfully recapitulate the heterogeneity of human tumors, there has been limited validation of the translational relevance of these models with respect to their fidelity to the intra- and inter-tumoral mutational heterogeneity that characterizes HCC as well as their ability to provide translationally reliable information for the design, testing and/or outcome evaluation of novel or existing therapies. Indeed, the creation of new patient-derived models of HCC requires rigorous validation of the resulting tumors to confirm their fidelity to the cancer of interest and robust credentialing criteria to ascertain their biological relevance and reliability as surrogates of patient response. In preliminary studies we have: 1) demonstrated the ability to generate PDXs and PDX-derived cell lines from percutaneous biopsies of tumors in patients with intermediate stage HCC and 2) developed methodologies to enable the characterization, validation and optimization of these models. The proposed project will build on this prior work to assess the fidelity and predictive potential of patient-derived models of HCC. We hypothesize that patient-derived models of HCC derived from percutaneous biopsies recapitulate the inter- and intra-tumoral heterogeneity of their parent biopsies and that these models are predictive of patient response to therapy. To test this hypothesis the proposed project will pursue three aims: (1) to define the representation of inter- and intra-tumoral clonal heterogeneity of patient-derived models of HCC through targeted sequencing and digital polymerase chain reaction; (2) to determine the predictive potential of patient-derived models of HCC for response to common HCC therapies; and (3) to investigate the role of HCC tumor initiating cells (TICs) in improving the yield and predictive potential of patient-derived models of HCC. Importantly, the achievement of the proposed aims will transform the utility of patient-derived models of HCC for translational research.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David E Kaplan其他文献

Top tagging: a method for identifying boosted hadronically decaying top quarks.
顶标记:一种识别增强强子衰变顶夸克的方法。
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    8.6
  • 作者:
    David E Kaplan;Keith R. Rehermann;Matthew D Schwartz;B. Tweedie
  • 通讯作者:
    B. Tweedie

David E Kaplan的其他文献

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{{ truncateString('David E Kaplan', 18)}}的其他基金

Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis
辛伐他汀对高危代偿性肝硬化受试者肝代偿失调和死亡的影响
  • 批准号:
    10578754
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis
辛伐他汀对高危代偿性肝硬化受试者肝代偿失调和死亡的影响
  • 批准号:
    10464880
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Cross-comparison of patient-derived xenografts and derivative organoids and cell lines for translational research in hepatocellular carcinoma
患者来源的异种移植物和衍生类器官和细胞系的交叉比较,用于肝细胞癌的转化研究
  • 批准号:
    9776808
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
B-Cell Dysregulation in Cirrhosis due to Chronic Hepatitis C Infection
慢性丙型肝炎感染引起的肝硬化中的 B 细胞失调
  • 批准号:
    8633581
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Tumor antigen-specific T-cells and hepatocellular carcinoma
肿瘤抗原特异性 T 细胞和肝细胞癌
  • 批准号:
    8438826
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Tumor antigen-specific T-cells and hepatocellular carcinoma
肿瘤抗原特异性 T 细胞和肝细胞癌
  • 批准号:
    8821484
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Engineered lymphocytes for the treatment of hepatocellular carcinoma
用于治疗肝细胞癌的工程化淋巴细胞
  • 批准号:
    8046329
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Engineered lymphocytes for the treatment of hepatocellular carcinoma
用于治疗肝细胞癌的工程化淋巴细胞
  • 批准号:
    7874043
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:

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